Retinol (vitamin A) and retinoic acid (vitamin A acid), their isomers, and certain of their analogues are known to play an essential role in controlling the normal differentiation of epithelial tissues and have therefore found use in controlling premalignant epithelial cell differentiation, as well as displaying beneficial effects in the treatment of acne and keratinizing skin disorders. However, a number of side effects complicate the administration of large doses of vitamin A. Hypervitaminosis A can be manifested as weight loss, desquamation of the skin, hair loss, irritation of the oral and pharyngeal mucosa, nose bleeds, headaches, bone pain, liver toxicity due to storage of vitamin A in the liver, papilledema, pseudotumor cerebri, demineralization and periosteal thickening of the bones. These difficulties, as well as the known toxicity of vitamin A and its analogues at high dosage level render these natural retinal compounds as well as their esters, acetates and palmitates undesirable for treatment of neoplastic or dermatopathic conditions.
Azulenic compounds are also known to have beneficial effects as anti-inflammatory, anti-dermatopathic, anti-allergenic, anti-tumorigenic and immunomodulatory agents, in addition to having applications in non-biological areas.
There is an on-going need for compounds, therapeutic compositions and methods for preventing and treating cancers and various dermatological disorders, which do not display the undesirable and toxic side-effects of vitamin A and related compounds.